There is still much heterogeneity in MSM adjusted for Breslow thickness, AJCC staging and Clark level, with no conclusive answers. Prospective studies are needed to clarify MSM for this specific patient group.Tumour-associated epilepsy accounts for a quarter of paediatric patients undergoing epilepsy surgery with the vast majority achieving long-term seizure and drug freedom. We report the case of an eight-year-old patient who presented with developmental delay and overgrowth, followed by temporal lobe seizures that were attributed to a mesio-temporal brain tumour, and who was eventually treated with epilepsy surgery. Histopathology revealed a diffuse astrocytoma but its gross total resection surprisingly failed to control the temporal lobe seizures. Genetic testing identified a de novo pathogenic variant in the NSD1 gene, thus establishing the diagnosis of Sotos syndrome. Sotos syndrome is a rare overgrowth syndrome with an increased incidence of malignancy, including the very rare occurrence of brain tumours. Seizures are frequent in patients with Sotos syndrome, often occurring with temporal lobe semiology and ictal EEG patterns in the absence of a brain lesion, and usually responding to anti-seizure medication. Our case highlights Sotos syndrome as a rare but important pitfall in the presurgical workup of temporal lobe epilepsy that should be considered particularly in MRI-negative cases but also in the presence of a focal lesion that does not fully explain the clinical picture. Most importantly, our observations underline the value of thorough presurgical diagnostics including genetic testing, even in apparently straightforward cases of lesional epilepsy, to rule out an underlying genetic aetiology that may not be treated by surgery. Finally, our findings emphasize the need to re-evaluate our less successful epilepsy surgery cases and offer informed counselling and prognostication.Merkel cell carcinoma (MCC) is an aggressive tumour that rapidly evolves to metastasis, however, paradoxically, complete spontaneous regression (CSR) of MCC has been reported. CSR may be linked to the presence of Merkel cell polyomavirus (MCPyV) combined with immune response tumour-infiltrating lymphocytes (TILs). To elucidate the mechanism of CSR by studying the profile of TIL infiltration and the role of MCPyV. We describe a clinical case of CSR with MCC and provide the results of a literature review based on PubMeb and Embase databases, from January 1st 1986 to April 1st 2010, using the terms "Merkel cell carcinoma" and "complete spontaneous regression". We found 38 clinical cases of CSR of primary MCC at different stages. The rate of MCPyV positivity was 75%, as found generally in MCC. https://www.selleckchem.com/products/lc-2.html The peritumoural infiltration was mostly composed by CD3+ T cells, whereas the intratumoural infiltration revealed CD8+ T cells, defined as TILs. To further investigate TILs in CSR of MCC, immunohistochemical staining was performed and compared to three non-regressive MCCs. CD8, IFN? and LAG3 expression was higher in biopsy samples with tumour regression, mainly inside the tumour nest. TILs were significantly more abundant in regressive MCC than in non-regressive MCC, in which both IFN? and LAG3 levels were low. This review and our clinical case confirms the central role of TILs in regressive MCC associated with IFN? and LAG3 secretion, thus underlining the interest in checkpoint inhibitors and adoptive T cell therapy in the treatment of MCC.Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17.5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies.Epstein-Barr virus (EBV) infection is associated with rheumatoid arthritis (RA) in adults, though the nature of the relationship remains unknown. Herein, we examine the contribution of viral infection to the severity of arthritis in mice. We provide the first evidence that latent gammaherpesvirus infection enhances clinical arthritis, modeling EBV's role in RA. Mice latently infected with a murine analog of EBV, gammaherpesvirus 68 (gHV68), develop more severe collagen-induced arthritis and a Th1-skewed immune profile reminiscent of human disease. We demonstrate that disease enhancement requires viral latency and is not due to active virus stimulation of the immune response. Age-associated B cells (ABCs) are associated with several human autoimmune diseases, including arthritis, though their contribution to disease is not well understood. Using ABC knockout mice, we provide the first evidence that ABCs are mechanistically required for viral enhancement of disease, thereby establishing that ABCs are impacted by latent gammaherpesvirus infection and provoke arthritis.Bacterial nutrition is a fundamental aspect of pathogenesis. While the host environment is in principle nutrient-rich, hosts have evolved strategies to interfere with nutrient acquisition by pathogens. In turn, pathogens have developed mechanisms to circumvent these restrictions. Changing the availability of bioavailable metal ions is a common strategy used by hosts to limit bacterial replication. Macrophages and neutrophils withhold iron, manganese, and zinc ions to starve bacteria. Alternatively, they can release manganese, zinc, and copper ions to intoxicate microorganisms. Metals are essential micronutrients and participate in catalysis, macromolecular structure, and signalling. This review summarises our current understanding of how central carbon metabolism in pathogens adapts to local fluctuations in free metal ion concentrations. We focus on the transcriptomics and proteomics data produced in studies of the iron-sparing response in Mycobacterium tuberculosis, the etiological agent of tuberculosis, and consequently generate a hypothetical model linking trehalose accumulation, succinate secretion and substrate-level phosphorylation in iron-starved M.